It has been estimated that 15% of couples will seek medical care at some time for infertility, and that a male factor will be important in 50% of the cases. Although the pathophysiology of most human male infertility is uncertain, the most common endocrine abnormality in men with impaired germ cell development is a rise in serum FSH levels. The long term goal of these studies is to understand this endocrine disturbance in infertile men. Aim 1 of the present proposal is to study the relationship between serum FSH and inhibin in infertile men by examining the nature of inhibin secreted by the testis in men with varicocele-associated infertility. Biochemical characterization of inhibin in spermatic vein blood 'in men with normal and increased levels of FSH will be performed to examine the hypothesis that various immunoreactive forms of inhibin with variable bioactivity are released by the human testis. Second, most of what is known about the cellular and molecular mechanisms by which inhibin and other testicular hormones regulate FSH is from studies in rats. Yet substantial differences in pituitary-testicular function in the rat and man have been identified, so that concepts developed from studies in rats may not be applicable to human male infertility. Accordingly, Aim 2 is to establish a model system using cultured pituitary cells from the nonhuman male primate in an effort to better understand FSH secretion in infertile men. Gonadotropin secretion and subunit messenger RNAs will be studied in pituitary cells in monolayer culture and in cells perfused with pulses of GnRH. The actions of inhibin, activin, follistatin, testosterone, dihydrotestosterone and estradiol on these cells will be examined.